Irritation of various mucous membranes can result from a variety of factors. On one hand, irritation may result from infections of the mucous membrane by a disease entity, such as occurs with strep throat. On the other hand, irritation of the mucous membranes can be caused directly by physical trauma to the mucous membrane, for example, by surgery or by abrasion from the insertion of a medical instrument. For example, the mucous membranes associated with the nasopharyngeal passage may be traumatized by insertion of a medical instrument such as a nasogastric tube, an anesthesia tube and the like. Types of surgery which can traumatize the nasopharyngeal passageway include tonsillectomies, tracheostomies, vocal cord surgery, etc. Here, irritation may occur to the buccal membrane, the oropharynx, the uvula, the trachea and/or the larynx.
Of particular concern to the present invention, however, is the trauma caused to the various tracheal mucosa resulting from endotracheal intubation which accompanies general anesthesia. Here, an endotracheal tube is inserted into the throat of a patient undergoing general anesthesia, and a cuff is inflated to block the air passageway. The anesthesia is administered through the endotracheal tube. This anesthesia technique can traumatize the tracheal mucosa in several ways. First, the physical rubbing of the endotracheal tube against the tracheal mucosa tends to irritate this mucous membrane. The irritation can be exacerbated by the inflation of the cuff provided on the device. Second, the tracheal mucosa may be damaged by the anesthesia itself or by desiccation from the anesthetic agent. As a result, the patient typically experiences extreme discomfort following anesthesia in the form of a painful sore throat, which condition may persist for several days.
Where a painful irritation of a mucous membrane results from a disease entity, it is not uncommon for a physician to prescribe a steroidal compound to alleviate the symptoms. One such example is the use of cortisone in cases where patient experiences extreme discomfort. The use of steroidal agents, however, are not generally prescribed for other trauma to a mucous membrane. Steroid compounds, of course, work by reducing swelling and have limited topical effect. They have the disadvantages of being slow acting or non-acting where the pain mechanism does not have associated swelling. Also, steroid compounds have the disadvantages of increasing the patient's susceptibility to secondary infections and having limited topical effect so that they are slow-acting. Topical anesthetics are sometimes are sometimes prescribed, such as xylocaine (viscous 4%), benzocaine and the like. Topical .anesthetics can work quickly, but are typically give relief for only a short duration.
Further, while various nonsteroidal anti-inflammatory agents are known, they are not prescribed for conditions of irritation to the mucous membranes, in general, or to the irritation of the tracheal mucosa resulting from intubation, in particular. Non-steroidal anti-inflammatory agents have long been prescribed for systemic use, but, except for a limited use in the eye, have not been used topically. One non-steroidal anti-inflammatory drug, diclofenac sodium, has been topically used as an ophthalmic for dilation of the eye but is known to desensitize the epithelial layer of the eye from pain caused by abrasion or other irritations, especially as may accompany surgery of the eye. Thus, diclofenac sodium is sometimes used topically in the eye for such purposes. Of course, the epithelial layer, however, is not a mucous membrane, such that the use of diclofenac sodium on a mucous membrane is not suggested by this known regimen. Indeed, the cellular structure differences between a mucous membrane and the corneal epithelium are substantial. The corneal epithelium is a stratified squamous epithelium having no secretory cells. A mucous membrane, however, contains a high percentage of secretory cells and is histologically distinct.
It is known that diclofenac sodium, that has a chemical formula of 2-[(2,6-dichlorophenyl) amino]benzeneacetic acid, monosodium salt; C.sub.14 H.sub.10 Cl.sub.2 NO.sub.2 Na, will penetrate various membranes, as described in "Human Transbuccal Absorption of Diclofenac Sodium From a Proto-type Hydrogel Delivery Device", Pharmaceutical Research, Vol. 10, No. 1 (1993). In this article, hydrogel disks were loaded with diclofenac sodium in methanol-water. The hydrogel disk was placed on a non-permeable patch and then affixed by dental adhesive to the center of the patient's cheek with a non-permeable patch so that the hydrogel contacted the buccal mucosa for a period of four hours. The purpose of the study was to determine if the diclofenac sodium would penetrate the membrane and enter the blood stream. Accordingly, blood was withdrawn from the volunteer at varying intervals and assayed. In each case, the volunteer for the study was healthy so that the buccal membrane was not previously traumatized, and the study was not directed to examine the effect of the diclofenac sodium on the buccal membrane or to evaluate any relief of irritation arising from the diclofenac sodium.
Accordingly, despite the various drugs available for the relief of irritation to mucous membranes, a need remains for agents which can adequately relieve pain and irritations to the mucous membranes without the disadvantages which accompany steroidal agents and existing topical anesthetics. Moreover, a long felt need has existed for a simple and effective technique of relieving irritation which results from the intubation of patients during anesthesia by relatively benign compounds.